Hacking the Bacterial Social Network

While we update our Twitters, Facebooks and Instagrams throughout the day, many might be unaware that a similar phenomenon is happening at the microbial level as well. In a two-part lecture, Bonnie Bassler, a professor and researcher at Princeton University, proposed that bacteria everywhere from the ocean to our gut relay and receive messages to one another through chemical signals. These signals help the bacteria know when to change their behaviour when other bacteria are around. For some, that means illuminating the marine darkness. For others, it means producing toxic chemicals to wreak havoc on our immune systems. Many disease-causing bacteria actually use this chemical network to sense when there are enough of their comrades before launching an attack against the immune system. But if the message can be sent, can it then be intercepted? In addition to presenting their previous research on what is currently known about this signaling system and combining several scientific disciplines, Bassler and her team worked with the bacterium that causes cholera to see if they could do just that.

Central to understanding the work of the researchers is the concept of quorum sensing. Bacteria have a chemical “language” that allows for communication with other members of the species, when they would otherwise be completely isolated from one another. When they receive messages from other bacteria, the bacteria then knows to modify its behaviour. Sometimes this means producing light, as the researchers found from their initial work with a species of marine bacteria. For others, the bacteria know to produce toxins that would otherwise be ineffective to carry out alone. Furthermore, bacterial species are able to transmit messages that can be received by other bacterial species as well. Long thought to be isolated but co-existing entities, Bassler and her associates proved that there is actually a bacterial nexus existing right beneath our eyes.

Armed with the knowledge of bacterial communication, Bassler and her team wanted to see if it was possible to hijack this communication network. Although the team initially worked with marine bacteria, Bassler turned her attention to the pathogenic bacteria that causes cholera, under the assumption that it uses the same chemical network as well. Cholera is a fast-disease that causes dehydration through extreme diarrhea, caused by the release of toxins by a certain species of bacteria. Though it often calls to mind images of a distant past, cholera still claims up to 120, 000 lives every year and can kill within hours after the onset of infection. Unlike some of the other known pathogens, the bacterium that causes cholera is most dangerous at low levels. When there are not too many other bacteria of the same species around, cholera-causing bacteria ramp up the productions of toxins that make us sick. When the numbers of bacteria increase, the cells send out a message to stop producing toxins and instead focus their attention towards infecting a new host.

For cholera-causing bacteria specifically, Bassler and her team wanted to see if they could send the cells false intelligence.  Bassler’s team wanted to manipulate experimental cells by sending them a synthetic signal to stop producing toxins while the cells were at low density. After isolating and characterizing what they believed to be this chemical signal responsible for turning off toxin-production, the team created a synthetic molecule that they hoped would mimic the actions of the real “off” signal.  When they added the synthetic molecule to cells infected with the bacteria, toxin production decreased dramatically.  The team then moved onto mice infected with cholera and saw similar drops in toxin levels. With the addition of the synthetic molecule, the researchers were able to restore the animals to health.

The team’s findings are incredibly exciting from a curative perspective. It implies that patients infected with the bacteria could be treated effectively and efficiently. However, the chemical mechanism this treatment does not necessarily work for all species of bacteria. The signaling system is complex and many other pathogens use the opposite mechanism whereby they are largely inactive but ramp up virulence at high densities. Therefore, instead of trying to mimic the chemical signal directly, researchers would need to create a synthetic antagonist (an off-switch) that is a molecule that would counteract the messenger rather than trying to duplicate the messenger itself. We should definitely take heart in the fact that some of the signals are species-specific. This has huge implications for the future of antibiotics. By finding ways to exploit signals for only one species, we can target harmful bacteria without the risk of also targeting good bacteria species or healthy tissue cells. Currently, antibiotics lack specificity and end up killing good and bad bacteria alike in addition to causing painful side-effects. By proposing a novel type of antibiotic, Bassler and her team may have laid the foundation to revolutionize the way that we treat diseases and lead to less noxious medications.